A class of amine derivatives, particularly aryl amine derivatives, of 4'-demethylepipodophyllotoxin compounds useful as anti-tumor agents has been described (see, for example, Lee, K.-H., et al., J Med Chem, 33:1364 (1990), and Lee, K.-H., et al., PCT patent application WO 90/09788).
The published syntheses of these compounds involves forming a mixture of .alpha. and .beta. epimers of 4'-0-demethyl-4-bromo-podophyllotoxin (4'-0-demethyl-4-bromo-desoxypodophyllotoxin), and reacting the mixture of epimers with a suitable amine, forming an epimeric mixture of the 4'-0-demethyl-4-amine-podophyllotoxin (4'-0-demethyl-4-amine-desoxypodophyllotoxin). The .alpha. and .beta. epimeric products are separated by chromatography. This method is suboptimal for large-scale production of the desired 4'-0-demethyl-4.beta.-amine-podophyllotoxin (4'-0-demethyl-4.beta.-amine-desoxypodophyllotoxin), because of the need for chromatographic separation of products.